title: Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells.
abstract: Invariant natural killer T cells (iNKT cells) can produce copious amounts of interleukin 4 (IL-4) early during infection. However, indirect evidence suggests they may produce this immunomodulatory cytokine in the steady state. Through intracellular staining for transcription factors, we have defined three subsets of iNKT cells (NKT1, NKT2 and NKT17) that produced distinct cytokines; these represented diverse lineages and not developmental stages, as previously thought. These subsets exhibited substantial interstrain variation in numbers. In several mouse strains, including BALB/c, NKT2 cells were abundant and were stimulated by self ligands to produce IL-4. In those strains, steady-state IL-4 conditioned CD8(+) T cells to become 'memory-like', increased serum concentrations of immunoglobulin E (IgE) and caused dendritic cells to produce chemokines. Thus, iNKT cell-derived IL-4 altered immunological properties under normal steady-state conditions.
authors.affiliation: The Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: You Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Keli L
authors.initials: KL
authors.lastname: Holzapfel
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhu
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jameson
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Hogquist
mesh_terms: D000367:Age Factors; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D014644:Genetic Variation / Q000276:immunology; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000276:immunology; D051379:Mice; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013045:Species Specificity; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D015703:Antigens, CD; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C513267:Zbtb16 protein, mouse; D015847:Interleukin-4; D007073:Immunoglobulin E